Oxalyl chloride → (S)-N-(5-chloro-pyridin-2-yl)-3-cyclohexyl-2-(8-methoxy-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-propionamide

Participants

Reaction Conditions

Reaction Steps

A solution of (S)-2-(8-methoxy-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-3-cyclohexyl-propionic acid (200 mg, 0.64 mmol) (from Example 7, Step 2c), in methylene chloride (10 mL) was treated with oxalyl chloride (0.07 mL, 0.64 mmol) at 0° C. The mixture was warmed to 25° C. and stirred for additional 2 hours. Then, the reaction mixture was cooled to 0° C., and N,N′-diisopropylethyl amine (0.34 mL, 1.92 mmol) and commercially available 5-chloro-pyridin-2-ylamine (83 mg, 0.64 mmol), were added. The reaction mixture was stirred for 16 hours at 25° C. The reaction mixture was diluted with water and extracted with ethyl acetate (2×). The combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo. The resulting residue, upon silica gel flash chromatography using hexane-ethyl acetate gradiant elution, afforded (S)—N-(5-chloro-pyridin-2-yl)-3-cyclohexyl-2-(8-methoxy-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-propionamide (68 mg, 26.3%), as a white solid. 1H NMR (DMSO-d6) δ: 11.07 (s, 1H), 8.39 (s, 1H), 8.04 (d, J=8.8 Hz, 1H), 7.90 (d, J=8.8 Hz, 1H), 7.22 (t, J=8.3 Hz, 1H), 6.77 (d, J=8.3 Hz, 1H), 6.68 (d, J=8.3 Hz, 1H), 5.07 (d, J=5.9 Hz, 1H), 4.37 (d, J=18.6 Hz, 1H), 4.03 (d, J=19.1 Hz, 1H), 3.82 (s, 3H), 3.55 (s, 2H), 1.48-2.00 (m, 7H), 0.85-1.32 (m, 6H).

Provenance & Evidence